2014
DHA-mediated enhancement of TRAIL-induced apoptosis in colon cancer cells is associated with engagement of mitochondria and specific alterations in sphingolipid metabolism.
SKENDER, Belma, Jiřina HOFMANOVÁ, Josef SLAVÍK, Iva JELÍNKOVÁ, Miroslav MACHALA et. al.Základní údaje
Originální název
DHA-mediated enhancement of TRAIL-induced apoptosis in colon cancer cells is associated with engagement of mitochondria and specific alterations in sphingolipid metabolism.
Autoři
SKENDER, Belma (203 Česká republika, domácí), Jiřina HOFMANOVÁ (203 Česká republika, domácí), Josef SLAVÍK (203 Česká republika), Iva JELÍNKOVÁ (203 Česká republika, domácí), Miroslav MACHALA, Marry Pat MOYER, Alois KOZUBÍK (203 Česká republika, domácí) a Alena HYRŠLOVÁ VACULOVÁ (203 Česká republika, garant, domácí)
Vydání
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, AMSTERDAM, ELSEVIER SCIENCE BV, 2014, 1388-1981
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
30105 Physiology
Stát vydavatele
Nizozemské království
Utajení
není předmětem státního či obchodního tajemství
Odkazy
Impakt faktor
Impact factor: 5.162
Organizační jednotka
Přírodovědecká fakulta
UT WoS
000340019800012
Klíčová slova anglicky
Docosahexaenoic acid; TRAIL; Apoptosis; Lipid metabolism; Colon cancer
Štítky
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 15. 6. 2020 17:42, Mgr. Marie Šípková, DiS.
Anotace
V originále
Docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid present in fish oil, may exert cytotoxic and/or cytostatic effects on colon cancer cells when applied individually or in combination with some anticancer drugs. Here we demonstrate a selective ability of subtoxic doses of DHA to enhance antiproliferative and apoptotic effects of clinically useful cytokine TRAIL (tumor necrosis factor-related apoptosis inducing ligand) in cancer but not normal human colon cells. DHA-mediated stimulation of TRAIL-induced apoptosis was associated with extensive engagement of mitochondrial pathway (Bax/Bak activation, drop of mitochondrial membrane potential, cytochrome c release), activation of endoplasmic reticulum stress response (CHOP upregulation, changes in PERK level), decrease of cellular inhibitor of apoptosis protein (XIAP, cIAP1) levels and significant changes in sphingolipid metabolism (intracellular levels of ceramides, hexosyl ceramides, sphingomyelines, sphingosines; HPLC/MS/MS). Interestingly, we found significant differences in representation of various classes of ceramides (especially C16:0, C24:1) between the cancer and normal colon cells treated with DHA and TRAIL, and suggested their potential role in the regulation of the cell response to the drug combination. These study outcomes highlight the potential of DHA for a new combination therapy with TRAIL for selective elimination of colon cancer cells via simultaneous targeting of multiple steps in apoptotic pathways.
Návaznosti
MUNI/A/0927/2013, interní kód MU |
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